Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-four patients with PSS were evaluated with regard to plasma concentration of blood coagulation and fibrinolysis factors: fibrinogen (Fbg), prothrombin time (PT), active partial thromboplastin time (APTT), protein C, thrombin-antithrombin III complex (TAT), antithrombin-III (AT-III), factor XIII (XIII) fibrinopeptide A (FPA), alpha 1-antitrypsin (alpha 1-AT), plasminogen (Pmg), alpha 2-plasmin inhibitor plasmin complex (PIC), alpha 2-plasmin inhibitor (alpha 2-PI), alpha 2-macroglobulin (alpha 2-MG), fibrinopeptide B beta 15-42 (FPB beta-15-42) and soluble fibrin monomer complex (SFMC), FDP (fibrin degradation product) and D-dimer. They were also evaluated with regard to platelet-derived proteins: beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), thromboxane B2 and 6-keto-prostaglandin F1 alpha (6KF). In the coagulation/fibrinolysis systems high plasma levels of TAT, AT-III, FPA, alpha 2-MG and FPB beta 15-42 could be demonstrated in more than 50% of total PSS patients. There was no statistical correlation between those of TAT and AT-III. Plasma levels of PIC, D-dimer, FDP and SFMC were not always high. There was no statistical correlation between those of TAT and PIC. These data lead us to consider that alpha 2-MG may play an important role for inhibiting PIC, which accelerates the conversion from fibrin into FDP. Subsequently, there were high plasma levels of FPB beta 15-42 converted from fibrin monomer. These data seem to be indicative of an involvement of coagulation and platelet disorder in PSS. These platelet-vessel system disorders might be closely related to the pathophysiology of PSS.
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PMID:Plasma levels of molecular markers of blood coagulation and fibrinolysis in progressive systemic sclerosis (PSS). 878 74

Since thromboembolic complications in transplanted patients are generally attributed to combined abnormalities in platelets and coagulo-lytic system, some hemostatic parameters tPA (tissue plasmogin activator):Ag and activity, its inhibitor-PAIAg and activity, tPA/PAI, thrombin-antithrombin (TAT) and plasmin-antiplasmin complexes (PAP), urokinase-uPA, euglobulin clot lysis time-ECLT, fibrinogen, plasminogen, protein C activity, D-dimer, prothrombin fragments1+2 (F1+2), fibrin monomers, fibronectin, lipoprotein-a, and von Willebrand factor(vWF), were evaluated using commercially available kits. The studies were performed on kidney transplant recipients treated with CsA, azathioprine and prednisone (n=21), and healthy volunteers (n=21). ECLT was significantly prolonged in kidney transplant recipients together with a rise in F1+2,lipoprotein-a, fibrinogen, fibronectin, and vWF when compared with controls. The TPA level was lower, whereas the PAI level was higher in kidney transplant recipients when compared with controls. In conclusion, CsA-treated kidney transplant recipients show evidence of pronounced impairment in fibrinolysis and endothelial damage in comparison with healthy volunteers.
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PMID:The coagulo-lytic system and endothelial function in cyclosporine-treated kidney allograft recipients. 882 84

We determined plasma levels of thrombomodulin, thrombin-antithrombin III complex (TAT), protein C, protein S, and plasmin-alpha 2 plasmin inhibitor complex (PIC) before and after hemodialysis in 54 patients receiving chronic hemodialysis, to evaluate the blood-coagulation system and to evaluate the antithrombogenicity of various dialyzer membranes. Predialysis levels of thrombomodulin and TAT were both significantly increased compared with normal control values, but levels of protein C, protein S, and PIC were not changed. In patients dialyzed with ethylene vinyl alcohol (EVAL) and polysulfone membranes, postdialysis levels of thrombomodulin, TAT, protein C, protein S, and PIC were not significantly different from the predialysis levels. However, in patients dialyzed with regenerated cellulose and polymethyl-methacrylate (PMMA) membranes, postdialysis levels of thrombomodulin, TAT, and PIC were significantly higher than predialysis levels. We conclude that patients on maintenance hemodialysis were considered to be in a state of hypercoagulability before hemodialysis, and a single hemodialysis session using regenerated cellulose and PMMA membrane may have caused injury to vascular endothelial cells, hypercoagulability, and enhancement of fibrinolytic activity.
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PMID:Evaluation of blood coagulation-fibrinolysis system in patients receiving chronic hemodialysis. 943 76

Barley serpin BSZx is a potent inhibitor of trypsin and chymotrypsin at overlapping reactive sites (Dahl, S.W., Rasmussen, S.K. and Hejgaard, J. (1996) J. Biol. Chem., in press). We have now investigated the interactions of BSZx with a range of serine proteinases from human plasma, pancreas and leukocytes, a fungal trypsin and three subtilisins. Thrombin, plasma kallikrein, factor VIIa/tissue factor and factor Xa were inhibited by BSZx at heparin independent association rates (k(ass)) of 4.5 X 10(3)-1.3 x 10(5) M(-1) s(-1) at 22 degrees C. Only factor Xa turned a significant fraction of BSZx over as substrate. Complexes of these proteinase with BSZx resisted boiling in SDS, and amino acid sequencing showed that cleavage in the reactive center loop only occurred after P1 Arg. Activated protein C and leukocyte elastase were slowly inhibited by BSZx (k(ass)=1-2 x 10(2) M(-1) s(-1)) whereas factor XIIa, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein and elastase were not or only weakly affected. The inhibition pattern with mammalian proteinases reveal a specificity of BSZx similar to that of antithrombin III. Trypsin from Fusarium was not inhibited while interaction with subtilisin Carlsberg and Novo was rapid but most BSZx was cleaved as a substrate. Identification of a monoclonal antibody specific for native BSZx indicate that complex formation and loop cleavage result in similar conformational changes.
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PMID:Inhibition of coagulation factors by recombinant barley serpin BSZx. 884 56

Excessive or nonphysiologic thrombogenesis and fibrinolysis accompanies many diseases. Several specific proteins involved in the physiologic regulation and maintenance of blood in a fluid state are reviewed in this article. Assays for these proteins or evidence of their function (antithrombin III, protein C, protein S, plasminogen/plasmin, tissue plasminogen activator, plasminogen activator inhibitor I, fibrinogen/fibrin degradation products, and thrombin/antithrombin complexes) are described. Principles, general methodology, and application in veterinary medicine are discussed. Although most of the investigative work and knowledge concerning these proteins and assays has been in human beings, their use and application in veterinary medicine is becoming more available in research laboratories at referral centers and some larger commercial veterinary laboratories. Use and interpretation of these assays will help clinicians and researchers better understand pathophysiologic processes occurring in various diseases associated with thrombogenesis and excessive fibrinolysis.
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PMID:Antithrombotic and fibrinolytic factors. A review. 886 93

A pathogenetic role for fibrin deposition and platelet activation in the kidney is thought to play a role in the pathogenesis of acute renal failure (ARF). Thus, some fibrinolytic parameters and platelet function have been studied in 17 patients with ARF and compared to healthy volunteers and subjects with chronic renal failure (CRF). Since serotonin may participate in pathological processes resulting from platelet/vessel wall interactions, its level in the whole blood and plasma was also assayed. In ARF and CRF platelet aggregatory responses in both whole blood and in platelet rich plasma upon stimulation with various agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those obtained in healthy volunteers. Increased levels of lipoprotein (a), von Willebrand factor (vWF) and fibronectin were found in ARF relative to controls. Protein C activity was significantly lower in patients with ARF. Euglobulin clot lysis time was prolonged in ARF and CRF, reflecting a decreased overall fibrinolytic activity. Activity of tissue plasminogen activator (tPA) inhibitor (PAI) and PAI:Ag were higher in ARF, whereas tPA:Ag, urokinase, tPA/PAI complexes, thrombin-antithrombin complexes (TAT), plasmin-antiplasmin (PAP) complexes, fibrinogen, and F1+2 did not differ between ARF and controls. In CRF elevated levels of TAT, PAP, fibrinogen and prothrombin fragments F1+2 were found, whereas concentration of fibronectin was lowered when compared to controls. In both groups of renal failure patients increased levels of fibrin monomers and d-dimer were found relative to healthy volunteers. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in patients with ARF and CRF relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with ARF and CRF. Chronic renal failure exhibit a slightly different pattern of coagulopathies that acute renal failure.
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PMID:Hemostasis, platelet function and serotonin in acute and chronic renal failure. 887 44

The kinetic parameters were determined for the hydrolysis of a peptide based on the activation site of the thrombin receptor (residues 38-60) by thrombin and 12 other proteases. The kcat and Km values for the cleavage of this peptide (TR39-40) by thrombin were 107 s-1 and 1.3 microM; the kcat/Km of TR39-40 is among the highest observed for thrombin. A model is presented that reconciles the parameters for cleavage of the peptide with the concentration dependence of cellular responses to thrombin. Cleavage of TR39-40 was not specific for thrombin. The pancreatic proteases trypsin and chymotrypsin hydrolysed TR39-40 efficiently (kcat/Km > 10(6) M-1.s-1). Whereas trypsin cleaved TR39-40 at the thrombin activation site (Arg41-Ser42), chymotrypsin hydrolysed the peptide after Phe43. This chymotryptic cleavage would result in inactivation of the receptor. The efficient cleavage of TR39-40 by chymotrypsin (kcat/Km approximately 10(6) M-1.s-1) was predominantly due to a low Km value (2.8 microM). The proteases factor Xa, plasmin, plasma kallikrein, activated protein C and granzyme A also hydrolysed TR39-40 at the Arg41-Ser43 bond, but exhibited kcat/Km values that were at least 10(3)-fold lower than that observed with thrombin. Both tissue and urokinase plasminogen activators as well as granzyme B and neutrophil elastase were unable to cleave TR39-60 at appreciable rates. However, neutrophil cathepsin G hydrolysed the receptor peptide after Phe55. Like the chymotryptic cleavage, this cleavage would lead to inactivation of the receptor, but the cathepsin G reaction was markedly less efficient; the kcat/K(m) value was almost four orders of magnitude lower than that for thrombin. In addition to the above cleavage sites, a secondary site for thrombin and other arginine-specific proteases was identified at Arg46, but the cleavage at this site only occurred at very low rates and is unlikely to be significant in vivo.
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PMID:Cleavage of the thrombin receptor: identification of potential activators and inactivators. 894 6

Studies on responses to surgical stress in blood coagulation and fibrinolysis, platelet counts and thromboxane B2 (TXB2) were carried out with 18 esophageal cancer patients who had undergone radical esophagectomy through right thoracotomy and reconstruction with gastric tube. Plasma levels were measured for the following for coagulation assessment: thrombin.antithrombin III complex (TAT), soluble fibrin monomer complex(SFMC), fibrinogen, antithrombin III, protein C and thrombomodulin. Selected fibrinolytic markers are: tissue plasminogen activator.plasminogen activator inhibitor 1 complex (tPA.PAI1C), plasminogen, alpha 2 plasmin inhibitor, plasmin. alpha 2 plasmin inhibitor complex(PIC), FDP and D-dimer. Peripheral venous blood samples were taken from the patients before the operation, immediately after the operation and on each of the first, second, third, seventh and fourteenth day after the operation. It was observed that TAT, SFMC, tPA.PAI-1C and TXB2 were remarkably altered immediately after the operation. This indicates that the major surgical stress significantly activated coagulation, fibrinolysis and platelets. Higher plasma levels of TAT compared to the pre-operation level was recorded for two weeks after the operation. Furthermore, in four cases, SFMC became positive during three to seven days after operation. These facts indicate that the activation of coagulation persisted during the days after operation. PIC began to increase from the 2nd to 3rd days after operation, reaching the maximum on the 7th day. Biphasic changes which peaked twice on the 1st and 7th days after operation were shown in plasma levels of FDP and D-dimer. These results indicate that the activation of fibrinolysis also persisted during the days after operation. The activation of coagulation and fibrinolysis may persist at least for two weeks after major surgical operation. Careful observation for the states of these systems was thought to be needed during the post-operative days, and the molecular markers could be useful to assess subclinical changes of these systems.
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PMID:[Responses to surgical stress in blood coagulation and fibrinolysis, platelet counts and thromboxane B2 after esophageal cancer operation]. 912 Oct 3

Hemodynamic forces modulate various endothelial cell functions even in the presence of cytokines under gene regulation. We have investigated the effect of shear stress on the coagulation and fibrinolysis systems in cultured human umbilical vein endothelial cells (HUVECs) perturbed by cytokines, using modified cone-plate viscometer. Thrombomodulin (TM), a surface glycoprotein receptor for thrombin that catalyzes the activation of the protein C anticoagulant pathway, and tissue factor (TF), a transmembrane glycoprotein that plays a central role in blood coagulation, are important regulators for coagulation in endothelium. Shear stress of 18 dynes/cm2 increased the expression of TM either in the presence or absence of TNF alpha (100 U/ml). In contrast, shear stresses of 6 approximately 24 dynes/cm2 decreased the expression of TNF alpha-induced TF in a shear intensity- and exposure time- dependent manner Tissue plasminogen activator(t-PA), which converts plasminogen to plasmin to degrade fibrin clot, and plasminogen activator inhibitor-1 (PAI-1), which inhibits t-PA function, play central roles in fibrinolysis in the endothelium. Treatment of the cells with IL-1 beta or TNF-alpha under static conditions had no effect on t-PA secretion, while release of PAI-1 increased. When cells were exposed to increasing shear stress up to 24 dynes/cm2, levels of t-PA significantly increased relative to shear stress, while PAI-1 secretion decreased gradually. In the presence of IL-1 beta or TNF-alpha, the increased production of t-PA was further augmented. These results clearly indicate that shear forces act as an important regulators of the coagulation and fibrinolysis systems in endothelium, to maintain antithrombogenicity of blood vessels.
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PMID:[Regulation of antithrombogenicity in endothelium by hemodynamic forces]. 913 94

Hepatic veno-occlusive disease (VOD) is a major complication after bone marrow transplantation (BMT). Its prediction, diagnosis and treatment remain unclear. Examination was made of changes in hemostatic parameters in patients with or without VOD after BMT. Twenty-seven children were studied following BMT. Eight of them developed VOD. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), von Willebrand factor (vWF), factor VII, fibrinogen (FBG), FDP, D-dimer (D-D), plasminogen (PLG), thrombin-antithrombin III (TAT), alpha 2-plasmin inhibitor/plasmin complex (PIC), antithrombin III (AT-III), protein C, N-terminal propeptide for type III procollagen (P-III-P), were measured weekly from pre-BMT to day 28 after BMT. In VOD patients, t-PA and PAI-1 significantly increased (P < 0.05) and FBG significantly fell during the post-transplant period (P < 0.05). Significantly low AT-III and PLG were also noted before VOD (P < 0.05). There were no changes in other hemostatic parameters. t-PA, PAI-1 and FBG would thus appear useful markers for the diagnosis of VOD, and AT-III and PLG, predictive markers for VOD. The coagulation-fibrinolysis system following endothelial cell damage may contribute to the onset of VOD.
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PMID:Changes in hemostatic parameters in hepatic veno-occlusive disease following bone marrow transplantation. 915 66


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